# US 12,180,300 B2 · Targeting moiety-drug grafted immune cell compositions and methods of use

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- Number: US 12,180,300 B2
- Document ID: US12180300B2
- Status: Granted
- Kind: B2
- Application number: 17/277,828
- Filed: 2019-09-20
- Published: 2021-11-18
- Granted: 2024-12-31
- Earliest claimed: 2018-09-20
- Assignees: Arizona Board of Regents on Behalf of the University of Arizona; University of Utah Research Foundation
- Applicants: Arizona Board of Regents On Behalf of the University of Arizona; University of Utah Research Foundation
- Inventors: Youngwook Won; David A. Bull; Daniel Yongwon Lee
- Web page: https://patentgrep.com/patent/US12180300B2

## CPC

- C07K 16/32: against translation products of oncogenes
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 47/68033: {the drug being a maytansine}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/6855: {the tumour determinant being from breast cancer cell}
- A61K 47/6901: {Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors}
- A61P 35/00: Antineoplastic agents
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/77: Internalization into the cell
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Surface-engineered immune cells, such as natural killer cells, grafted with targeting moiety-drug complexes. The present invention combines chemotherapy and immunotherapy by engineering the immune cells to target specific tumor cells through antigen recognition and deliver potent chemotherapeutic agents, thereby destroying the tumor cells. The surface-engineered immune cells may be prepared using a one-step method. The present invention also provides kits for preparing the surface-engineered immune cells.

## Claims

### Claim 1

A chemoimmunotherapeutic composition for targeting a HER2 expressing cancer cell, said composition comprising:
a) a targeting moiety specific for and capable of binding to a target on a cell of interest, wherein the targeting moiety is trastuzumab;
b) a drug conjugated to the targeting moiety forming a targeting moiety-drug complex, wherein the drug is emtansine (DM1);
c) a phospholipid linked to a polyethylene glycol (PEG) forming a phospholipid-PEG linker, wherein the phospholipid-PEG linker is attached to the targeting moiety-drug complex; and
d) an immune cell, wherein the targeting moiety-drug complex is hydrophobically bound to the immune cell via the phospholipid-PEG linker, wherein the immune cell is a natural killer (NK) cell;
wherein the targeting moiety-drug complex directs the immune cell to the cell of interest,
wherein the drug has a cytotoxic effect on the cell of interest.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the phospholipid is selected from the group consisting of 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine and 1,2-distearoyl-sn-glycero-3-phosphocholine.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the PEG has a molecular weight from 2 kDa to 10 kDa.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the cell of interest is a breast cancer cell.

### Claim 5

A method of treating a HER2 expressing tumor in a subject in need thereof, comprising administering a chemoimmunotherapeutic composition comprising:
a) a targeting moiety specific for and capable of binding to a target on a cell of interest wherein the targeting moiety is trastuzumab;
b) a drug conjugated to the targeting moiety forming a targeting moiety-drug complex, wherein the drug is emtansine (DM1);
c) a phospholipid linked to a polyethylene glycol (PEG) forming a phospholipid-PEG linker, wherein the phospholipid-PEG linker is attached to the targeting moiety-drug complex; and
d) an immune cell, wherein the targeting moiety-drug complex is hydrophobically bound to the immune cell via the phospholipid-PEG linker, wherein the immune cell is a natural killer (NK) cell;
wherein the targeting moiety-drug complex directs the immune cell to the cell of interest,
wherein the drug has a cytotoxic effect on the cell of interest.

### Claim 6 (depends on 5)

The method of claim 5, wherein the phospholipid is selected from the group consisting of 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine and 1,2-distearoyl-sn-glycero-3-phosphocholine.

### Claim 7 (depends on 5)

The method of claim 5, wherein the PEG has a molecular weight from 2 kDa to 10 kDa.

### Claim 8 (depends on 5)

The method of claim 5, wherein the cell of interest is a breast cancer cell.
